miR-184 promotes compensatory lung growth via TIMP-2/MMP-14 in pneumonectomy model
10.3969/j.issn.1000-4718.2023.12.012
- VernacularTitle:miR-184通过TIMP-2/MMP-14促进PNX模型中代偿性肺生长
- Author:
Jing PENG
1
;
Xudong XIANG
;
Zhonghui WANG
;
Qiongchuan WANG
;
Shi-Hao SHAO
;
Weihao MA
;
Bobo ZHU
;
Li ZHAO
Author Information
1. 昆明医科大学第三附属医院(云南省肿瘤医院)麻醉科,云南 昆明 650118
- Keywords:
multiple primary lung cancer;
compensatory lung growth;
pneumonectomy;
microRNA-184;
tis-sue inhibitor of metalloproteinase-2;
matrix metalloproteinase-14
- From:
Chinese Journal of Pathophysiology
2023;39(12):2214-2222
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To explore the effect of microRNA-184(miR-184)on compensatory lung growth(CLG)af-ter lobectomy in multiple primary lung cancer(MPLC)and its mechanism.METHODS:(1)Lung tissue samples(n= 16)from MPLC patients and patients with good recovery after lobectomy(CLG)were collected,and the expression of miR-184 was measured by RT-qPCR.(2)Human alveolar epithelial cells were divided into NC-mimic group,miR-184 mimic group,OE-NC group,tissue inhibitor of metalloproteinase-2(TIMP-2)overexpression(OE-TIMP-2)group,and miR-184 mimic+OE-TIMP-2 group according to the transfection(n=3).The expression of miR-184,TIMP-2 mRNA and matrix metalloproteinase-14(MMP-14)mRNA was measured by RT-qPCR,and the protein expression of TIMP-2 and MMP-14 was determined by Western blot.The proliferation of the cells was measured by CCK-8 and colony formation assays.(3)C57BL/6J mice were divided into pneumonectomy(PNX)group and PNX+miR-184 mimic group(n=5).The flexiVent system was used to measure the vital capacity and lung compliance of the mice.Lung volume was measured by water dis-placement method,and lung tissue changes were observed by HE staining.RESULTS:The expression of miR-184 was significantly higher in the patients with better recovery after lobectomy(P＜0.01).Overexpression of miR-184 promoted the proliferation of human alveolar epithelial cells and the recovery of lung function in mice after PNX.In terms of mecha-nism,miR-184 showed targeted binding with TIMP-2,and overexpression of miR-184 promoted the expression of MMP-14 by inhibiting TIMP-2,thereby promoting the proliferation of human alveolar epithelial cells and the recovery of mouse lung function after PNX.CONCLUSION:miR-184 promotes CLG after PNX through the TIMP-2/MMP-14 axis.
